Enhanced activation of the median pre‐optic nucleus contributes to the activation of the paraventricualr nucleus in heart failure

The purpose of the study was to determine if altered median pre‐optic nucleus (MnPO) mediated input to the paraventricular nucleus (PVN) results in increased renal sympathetic nerve activity (RSNA) in rats with chronic heart failure (HF). The left coronary ligation‐induced HF model in the rat was used. In the MnPO, FosB immunoreactivity (a marker for neuronal activation) increased significantly in HF rats compared to sham‐operated rats. In alpha‐chloralose and urethane anesthetized Sprague Dawley rats, microinjection of N‐methyl‐D‐aspartic acid (NMDA, 50–200pmol) into the MnPO produced dose‐dependent increases in RSNA, blood pressure (BP) and heart rate (HR) (n=6/group) in both sham‐operated and HF rats. The response to NMDA was significantly potentiated (50% at highest dose) in HF rats compared with sham‐operated rats. On the other hand, microinjection of the NMDA receptor antagonist AP5 (4–16nmol) into the MnPO caused decreases in RSNA, BP and HR only in rats with HF but not in sham‐operated rats. Furthermore, prior microinjection of AP5 (4nmol, bilaterally) into the PVN was able to significantly blunt the responses to NMDA in the MnPO. These data indicates that a higher forebrain site (MnPO) contributes to the sympatho‐excitation observed during late stages of HF via increased neuronal activity within the PVN.